Research Paper Volume 12, Issue 23 pp 24184—24207

Construction of circRNA-based ceRNA network to reveal the role of circRNAs in the progression and prognosis of metastatic clear cell renal cell carcinoma

Xiyi Wei1, *, , Yuxiang Dong1,2, *, , Xinglin Chen1, *, , Xiaohan Ren1, *, , Guangyao Li1, , Yamin Wang1, , Yichun Wang1, , Tongtong Zhang1, , Shangqian Wang1, , Chao Qin1, , Ninghong Song1,3, ,

  • 1 The State Key Lab of Reproductive, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • 2 First Clinical Medical College of Nanjing Medical University, Nanjing 210029, China
  • 3 The Affiliated Kezhou People’s Hospital of Nanjing Medical University, Kezhou, Xinjiang 845350, China
* Equal contribution

Received: June 3, 2020       Accepted: August 8, 2020       Published: November 20, 2020
How to Cite

Copyright: © 2020 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


CircRNAs are now under hot discussion as novel promising bio-markers for patients with clear cell renal cell carcinoma. The purpose of our study is to identify several circRNAs related to the metastasis and progression of clear cell renal cell carcinoma, and to further investigate the mechanism of their influence on tumor progression. The transcriptome data of ccRCC and clinical characteristics used in this study were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus database. A total of 114 circRNAs were found to be related to tumor initiation, progression and metastasis after the intersection. In addition, 14 miRNAs and 201 eligible mRNAs were selected as targets gene, respectively. CeRNA network was constructed based on 8 circRNAs, 14 miRNAs, and 201 mRNAs. Besides, another 6 hub genes were identified via the PPI network. It should be noted that only TRIM2 was confirmed as an independent prognostic factor, which was simultaneously significantly related to both clinical stage and pathological grade in clinical cohorts. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated the possible function of TRIM2 in ccRCC progression, such as ubiquitin mediated protein hydrolysis, cell adhesion molecules, Th17 cell differentiation signaling pathway and so on. Gene set enrichment analysis analysis revealed that TRIM2 may be involved in ubiquitin mediated proteolysis, apoptosis, autophagy and citrate cycle TCA cycle. Hub circ_RNAs expressions were validated in ccRCC tissues and cell lines. Our study revealed that the hsa_circ_0002286 / has-mir-222-5p / TRIM2 axis played a critical role in the progression of ccRCC. Specifically, it may inhibit the metastasis and progression of ccRCC, which could serve as a potential therapeutic target.


ccRCC: clear cell renal cell carcinoma; RCC: renal cell carcinoma; ncRNA: non-coding RNA; circRNAs: Circular RNAs; DECs: differentially expressed CircRNAs; GEO: Gene Expression Omnibus; MRE: microRNA response element; CSCD: Cancer-Specific CircRNA database; TCGA: The Cancer Genome Atlas; KIRC: kidney renal clear cell carcinoma; DEmiRs: differentially expressed miRNAs; DEmRs: differentially expressed mRNAs; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; BP: biological process; CC: cellular components; MF: molecular function; OS: overall survival; GSEA: Gene set enrichment analysis; GDSC: Genomics of Drug Sensitivity in Cancer; HPA: Human Protein Atlas; FSCN1: fascial-actin-binding-protein 1; HCC: hepatocellular carcinoma; CAMs: cell adhesion molecules; Th17: T-helper 17; TME: tumor micro-environment; STRING: Search Tool for the Retrieval of the Interacting Genes; RT-qPCR: reverse transcription and quantitative PCR; KM: Kaplan-Meier; RBP: RNA binding protein; ORE: open reading frame; ES: Enrichment score; NES: Normalized enrichment score; FDR: False discovery rate.